Globally, tuberculosis (TB) is the most serious ongoing airborne infectious threat, but there has been recent concern about the airborne spread of influenza, SARS, and certain bioterrorism agents. While the domestic risk of TB transmission for health care workers has fallen, it remains higher than the general population. US medical, humanitarian, and research workers as well as students are increasingly exposed to drug resistant TB abroad. Prevention has depended on a hierarchy of traditional control measures, but these have been poorly implemented where they are needed most, and there have been no truly novel advances in transmission controls for over 50 years. Airborne TB is a prototype for other airborne infectious agents. Because M. tuberculosis is an environmentally hearty airborne agent, interventions that reduce airborne TB are likely to be even more effective against less environmentally well-adapted agents such as influenza. In our previous NIOSH grant we established a quantitative air sampling facility in South Africa using multidrug resistant (MDR) tuberculosis as a surrogate airborne organism. We showed that upper room ultraviolet (UV) air disinfection was 80% effective and that the use of surgical masks on TB patients was 50% effective in reducing transmission to highly susceptible sentinel guinea pigs breathing exhaust air from the ward. In this renewal grant application, we propose to use exactly the same proven quantitative air sampling methods to test three novel interventions to protect workers and other building occupants: 1) a new, more energy efficient upper room UV air disinfection system, 2) triethylene glycol (TEG) vapor as a safe chemical air disinfectant, and 3) an inhaled cationic salt solution (ICSS) to reduce production of exhaled infectious droplets. We will also test the effects of high humidity on UV air disinfection and conduct exploratory molecular-based air sampling in parallel with guinea pig air sampling. A major limitation of upper room UV air disinfection is cost contributed to by the highly inefficient tightly louvered UV fixtures currently used to prevent excessive UV in the lower room. A totally new approach to upper room UV air disinfection addresses both efficacy and safety. The inhaled salt solution is isotonic saline, a prototype for several cationic salts shown to reduce the generation of airborne particles by changing the mechanical properties of the fluid normally lining the central airways. This will be the first quantitative test of the impact of inhaled cationic salts in reducing airborne infection generated by human sources. TEG vapor was extensively studied as an air disinfectant from 1941-1952 with highly encouraging experiments published in Science and other prestigious journals. The EPA has determined that it is safe for prolonged human and animal exposure at the very low levels required (parts 1:7 million per by volume), and it continues to be found today in over-the-counter disinfectant sprays. Under experimental conditions, TEG vapor proved rapidly effective against a long list of test microorganisms. New particle generating and monitoring technologies have solved other practical problems applying TEG. PUBLIC HEALTH RELEVANCE: Airborne infections are on ongoing threat to the workplace both in the US and globally. Having shown that ultraviolet air disinfection is 80% effective against tuberculosis transmission, and that masks on patients are 50% effective, this research project will similarly test three novel interventions: 1) a new, more energy-efficient upper room UV system, 2) inhaled cationic salt solution (normal saline) in order to reduce the production of airborne droplets by infectious patients, and 3) triethylene glycol (TEG) vapor, a commonly used disinfectant, using a novel vapor generating and monitoring system.